tbuckley/cabot-search huggingface dataset:
Safety, efficacy, and clinical outcomes of the anti-CCR5 inhibitor (Leronlimab): A pooled analysis of three clinical trials in patients with mTNBC.
Authors: Daniel L Adams, Ashvathi Raghavakaimal, Cha-Mei Tang, Kirby P Gardner, Scott Kelly, Nader Pourhassan, Nitya Ray
Journal: Journal of Clinical Oncology (2022)

e13062 Background: Metastatic triple negative breast cancer (mTNBC) is a highly invasive BC subtype with limited treatment options and poor clinical outcomes. Leronlimab, a humanized IgG4κ antibody, competitively inhibits CCR5, a cancer motility receptor and target for cancer inhibition. We report on a pooled analysis of n = 28 mTNBC patients (pts) showing that leronlimab has potent antitumor activity with improved 1 year progression free (PFS) &amp; overall survival (OS) with few treatment emergent adverse events (TEAEs). Further, we explored the effect of leronlimab on circulating tumor associated cells (TACs) from peripheral blood as a surrogate and early predictor of drug response. Methods: mTNBC pts results from 3 blinded prospective clinical drug studies, Phase 1b/2 dose escalation (NCT03838367), Compassionate Use (NCT04313075), and Basket Study (NCT04504942) were pooled to evaluate leronlimab’s safety &amp; efficacy at 12 months (mos). Pts received ≥1 dose of leronlimab alone (n = 2), with carboplatin (n = 11) or with physician’s choice (n = 15). Pts received 1-33 doses, ranging from 350mg (n = 9), 525mg (n = 16) or 700mg (n = 3). In addition, anonymized pt peripheral blood was procured before and after (̃30 days) induction as an exploratory biomarker, to evaluate TACs in predicting efficacy. Progressive disease, stable disease or partial response was determined by RESICT v1.1, and univariate analysis was used evaluate PFS &amp; OS. Results: mTNBC pts were pooled from Phase 1b/2 (n = 10), Compassionate Use (n = 16), and Basket Study (n = 2) treated with 350-700mg doses, 4 pts escalating 350 to 525mg. Pts had 1-5+ prior systemic therapies for mTNBC (median = 2), median age 52 (range 33-84), ECOG 0 (n = 18) or ECOG 1 (n = 10), n = 17 had visceral mets, and n = 6 had brain mets. A total of n = 68 TEAEs were reported, with n = 7 grade I/II &amp; n = 1 grade III related to leronlimab. At 12 mos, pts had a mPFS = 3.8 mos (95%CI 2.3-6.2) and mOS = 6.6 mos (CI95% 4.9-12+). However, pts treated with 525-700 mg doses (n = 19) had a &gt; 75% improved mPFS = 6.1 mos (95%CI 2.3-7.5) and mOS 12+ mos (95%CI 5.5-12+). Further, a drop in circulating TACs was identified in 75% (n = 21/28) pts and predicted for significantly better clinical outcomes, mPFS = 6.2 and mOS &gt; 12 mos. Conclusions: These studies suggest that mTNBC pts dosed with leronlimab had high clinical benefit, i.e. longer PFS &amp; OS with few TEAEs, and leronlimab resulted in a drop in circulating TACs in the majority of pts correlating with early therapy response. Clinical trial information: NCT03838367, NCT04313075, NCT04504942.
Serial genomic analysis of circulating tumor cells and circulating tumor DNA in triple-negative and HER2-positive advanced, metastatic breast cancer.
Authors: Ji Eun Lee, Kabsoo Shin, Seung Yeon Joe, Hayoon Lee, Junghoon Park, Byung Hee Jeon, Ahwon Lee
Journal: Journal of Clinical Oncology (2022)

e12561 Background: Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have a promising role for detecting early response and progression in breast cancer. We performed serial genomic analysis of CTC and ctDNA in advanced, metastatic triple negative breast cancer (TNBC) and HER2 positive breast cancer (BC). Methods: Serial CTCs, ctDNA were prospectively collected in 9 early or advanced, and 10 metastatic BC patients periodically during systemic chemotherapy. CTC was isolated from whole blood through EpCAM positive bead selection, and ctDNA was isolated from plasma. For genomic profiling of CTC and ctDNA, Oncomine™ Comprehensive Assay Plus and Oncomine™ Pan-Cancer cfDNA assay (included BRCA1, BRCA2 and MYCN customized panel) was performed and analyzed, respectively. Results: TP63 was most commonly detected mutation (13 patients, 68.4%) at serial CTC analysis with median variant of allele frequency (VAF) of 18.6% (range 11.5̃25.2%), irrespective of tumor subtype and stage. In ctDNA analysis, 11 patients showed TP53 mutation with low VAF (median 1.4%, range 0.3̃12.3%). FGFR4 was equally detected, with median variant of allele frequency (VAF) of 57.2% (range 46.6-99.8) and there was no change of FGFR4 VAF irrespective of tumor response in CTC analysis. In three gBRCA1 mutated patients, BRCA1 was identically detected in 3 patients based on CTC analysis and in 2 patients based on ctDNA analysis with VAF of approximately 50%. There were no significant changes of VAF in target mutations of CTC irrespective of tumor response and subtype. In TNBC patients who received neoadjuvant chemotherapy, tumor mutation burden (TMB) showed gradual decrease during treatment. However, there were initial surge of TMB in HER2 positive BC patients who received neoadjuvant chemotherapy, irrespective of presence of pathologic complete response. Conclusions: Our study suggest that serial follow up CTC and ctDNA is feasible and reflect the general characteristics of baseline characteristics and dynamic molecular alteration of breast cancer. Further analysis with larger patient sample and correlation with tumor tissue is warranted in the future.
Blood-borne assessment of stromal activation in esophageal adenocarcinoma to guide tocilizumab therapy: A randomized phase II proof-of-concept study (NCT04554771).
Authors: Benthe Doeve, Roos E. Pouw, Mark I. Van Berge Henegouwen, Maarten C.C.M. Hulshof, Jan Paul Medema, Sarah Derks, Maarten F. Bijlsma, Hanneke W.M. Van Laarhoven
Journal: Journal of Clinical Oncology (2022)

TPS4166 Background: The tumor stroma is increasingly acknowledged to harbor tumor-promoting properties. Recently, we found that stroma activity measured by serum ADAM12 predicts response to chemoradiation in esophageal adenocarcinoma (Veenstra et al., Oncogenesis, 2018). Preclinically, the esophageal adenocarcinoma stroma was found to produce interleukin 6, which causes epithelial-to-mesenchymal transition of tumor cells. These mesenchymal tumor cells have a poor response to chemoradiation (Ebbing et al., PNAS, 2019). Therefore, stroma-derived interleukin 6 provides a potential new target to improve the treatment of esophageal adenocarcinoma. Tocilizumab is an interleukin 6 receptor inhibitor clinically used in rheumatoid arthritis and cytokine-release syndrome. In this phase II proof-of-concept clinical trial, we aim to demonstrate that stroma-targeting by tocilizumab in esophageal adenocarcinoma patients with highly activated stroma increases efficacy of chemoradiation measured by pathological response according to the Mandard criteria. Methods: BASALT is a multi-center, randomized, open-label phase II proof-of-concept clinical trial in patients with surgically resectable adenocarcinoma of the esophagus or gastroesophageal junction (NCT04554771). To assess efficacy of tocilizumab in addition to chemoradiation, 48 patients will be grouped for serum ADAM12 level with a cutoff of 203 pg/mL. Patients are then randomized in a 1:1:1:1 ratio to receive three cycles of tocilizumab every two weeks in addition to paclitaxel, carboplatin and radiation (Table). The sample size is based on the rule-of thumb estimate of 12 patients per arm. Tocilizumab will be given intravenously at a dose of 8 mg/kg with a maximum of 800 mg per dose. Efficacy will be assessed by pathological response to chemoradiation according to the Mandard criteria. Secondary endpoints are overall and progression free survival, safety and toxicity, feasibility and efficacy of interleukin 6 inhibition with serum interleukin 6 levels, immunohistochemistry and RNA-sequencing. Currently, 28 out of the 48 planned patients have been enrolled. Clinical trial information: NCT04554771. [Table: see text]
A multicenter evaluation of treatment patterns and outcomes for Adamantinoma-like Ewing sarcoma.
Authors: Rodney Dixon Dorand, Daniel Ying Wang, Vicki Leigh Keedy, Elizabeth J. Davis
Journal: Journal of Clinical Oncology (2022)

e23500 Background: Sarcomas are a rare and heterogenous group of malignancies comprised of &gt; 150 histologic subtypes. Adamantinoma-like Ewing sarcoma (ALES) is a rare, small round blue cell tumor that represents a variant of Ewing sarcoma (EWS). First described 20 years ago, ALES harbors a EWS subset defining EWS-related translocation; however, ALES has a complex epithelial differentiation component defining it as a distinct clinical entity. Most ALES cases arise in the head and neck, but it has also been reported in the extremities and thorax. Given the rarity of ALES, there is a paucity of literature to guide treatment and describe outcomes. Methods: We performed a retrospective review (January 1, 2010-January 1, 2022) at two sarcoma centers in the United States and identified 4 cases of ALES. Tumor and patient characteristics were described, and patient outcomes were assessed. Results: Four patients were identified. 3 (75%) were male. Median age at diagnosis was 37 years (range 23-57). Primary site of ALES was head and neck (50%) and thorax (50%). Median tumor size was 4 cm (2.7-5.5 cm). All patients underwent resection of their primary tumor, and two (50%)received adjuvant radiation therapy. All pts received/are receiving adjuvant chemotherapy. 75% of patients were treated with Vincristine, Doxorubicin, and Cyclophosphane (VDC) alternating with Ifosfamide &amp; Etoposide (IE) for 12-14 cycles. One patient received 4 cycles of adjuvant carboplatin and etoposide and radiation after an initial diagnosis of basaloid carcinoma but recurred 47 months later and diagnosed at ALES at that time. That patient underwent re-resection followed by adjuvant chemotherapy with Vincristine, Doxorubicin, and Ifosfamide (VAI). Median follow-up from initial diagnosis was 25 months (3-39 months). All patients are alive with no evidence of disease. Conclusions: Similar to treatment of EWS, a multidisciplinary strategy is paramount. VDC/IE is a reasonable treatment strategy. Further multicenter collaboration is essential to define clinical characterization of this rare sarcoma subtype and to guide treatment particularly in the relapsed or refractory setting.[Table: see text]
Patient-reported reasons for no-shows to screening mammogram appointments among African American women.
Authors: Whitney L Hensing, Yu Tao, Chaelee Park, Dori Redding, Teresa Arb, Pechaz Clark, Stephanie White, Tess Thompson, Foluso Olabisi Ademuyiwa
Journal: Journal of Clinical Oncology (2022)

e18534 Background: Mammography screening significantly reduces breast-cancer related mortality; however, many women fail to undergo screening as recommended by national guidelines. No-shows are responsible for a significant proportion of delayed or missed cancer screening exams. Further, no-shows disproportionately affect underserved and minority populations. We previously identified a high no-show rate for screening mammograms among patients seeking care our institution. African American (AA) women were almost three times more likely to no-show than non-Hispanic white women. The racial disparity in no-shows persisted after adjustment for socioeconomic factors. The objective of this survey study was to identify reasons for missed mammogram screening appointments among AA women. Methods: We conducted a survey (via mail or telephone) of AA women who missed their screening mammogram appointment in summer 2021. Using a structured survey instrument, we collected information on patient-specific and health service barriers. Patient-specific barriers included procedure-related concerns (e.g., concern about discomfort), cognitive-emotional factors (e.g., fear of finding cancer), and changes in health status. Health service barriers included logistical factors (e.g., transportation), cost (e.g., lack of insurance) and scheduling problems (e.g., forgot about appointment or scheduled at an inconvenient time). Here we describe the most common reasons for missed appointments and compared women who reported patient-specific versus health service barriers. Results: 255 women who no-showed for their appointment were contacted and 91 participated in the study survey (35.6% response rate). Most respondents (90%) attributed their no-show to at least one of the listed barriers. Nineteen (7.5%) attributed their no-show to COVID-19, but only 1 person reported this as their only barrier. Scheduling issues were the most commonly reported barriers (57.8%), followed by transportation (38.9%). Three-quarters of respondents reported health service barriers, while only 40.7% reported patient-related barriers. The most common patient-related barriers were cognitive-emotional (25%), changes in health status (20.9%) and procedure-related concerns (15.6%). The majority of respondents (82.6%) were interested in rescheduling their mammogram. Conclusions: Most appointment no-shows among surveyed AA women resulted from potentially preventable scheduling and transportation issues. Relatively few respondents reported cognitive-emotional or procedure-related concerns. Further, the majority of respondents were interested in rescheduling their mammogram; which suggests that these women remain motivated to undergo breast cancer screening. Programs which address preventable health-service related issues may help these women keep their appointments.
Treatment patterns of patients with glioblastoma multiforme in the real-world setting in a developing country.
Authors: Juan José Sánchez Hernández, Santiago Zarroca Palacio, Raul Rogelio Trejo Rosales, Yuly Andrea Remolina Bonilla, Dulce Angelica De Jesus Hernandez, Miriam Najar, Nestor Javier Lizcano Aguilar, Marco Antonio Hernandez Castillo, Andrea Cruz, Amairany Guadalupe Vélez Martínez, Eduardo Sanchez, Karina Morales Hernández, Angel Gabriel Ignacio Irigoyen Álvarez
Journal: Journal of Clinical Oncology (2022)

2067 Background: Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor. Surgery followed of temozolomide administered concurrently with radiation therapy (RT) and followed by adjuvant temozolomide for six cycles significantly improved survival compared with radiation therapy alone in a randomized controlled trial published by Stupp and colleagues. Real world evidence in patients with GBM is scarce in Latin America. Methods: A retrospective study was conducted at the Hospital de Oncología, Centro Médico Nacional Siglo XXI, a referral center in Mexico City. We included histologically confirmed patients with GBM treated in a period from January 2015 to January 2019. Descriptive statistics and Kaplan-Meier method with log-rank were used for analysis. Cox regression was used for multivariate analysis. Results: A total of 184 patients were included, 96 were men (52,2%) and 88 were women (47.8%); median age was 56 years (range 18 - 87). ECOG performance status scale 0-1, and ≥ 2 represented 34.2% and 65.8% of the cohort, respectively. Maximal surgical resection was performed in 172 patients (93%). After surgery or biopsy, 12 patients (6.5%) did not receive any subsequent oncology treatment. Treatment with concomitant RT with TMZ was offered to 156 patients (84.4%) and RT alone to 16 patients (8.7%). The most common RT modality was conventional fractionation (60 Gy in 30 fractions) in 75% of cases. After concurrent therapy, 135 (86.5%) received adjuvant TMZ, of which 53.4% received ≤ 5 cycles and 46.6% received ≥ 6 cycles. The median overall survival of the entire cohort was 20.1 months (95% CI 13.3 - 26.9 months). Survival in patients with adjuvant TMZ was superior versus patients who did not receive complete multimodal treatment (26.3 months vs 10.5 months, p &lt; 0.001). In the multivariate analysis, adjuvant chemotherapy was the only independent factor with statistical significance HR 0.18 (95% CI, 0.08 to 0.41 [p &lt; 0.001]). Conclusions: In this retrospective study our data confirm that receiving adjuvant TMZ treatment is beneficial in prolonging overall survival compared to those who do not receive adjuvant therapy in patients with GBM.
A phase 3 study of the subcutaneous programmed cell death protein 1 inhibitor sasanlimab as single agent for patients with bacillus Calmette-Guérin, unresponsiv,e high-risk, non-muscle invasive bladder cancer: CREST Study Cohort B.
Authors: Neal D. Shore, Thomas Powles, Jens Bedke, Matt D. Galsky, Evgeny Kopyltsov, Andrea Necchi, Joan Palou, Jennifer J. Vermette, Alison E. Randall, Kristen J. Pierce, Rossano Cesari, Gary D. Steinberg
Journal: Journal of Clinical Oncology (2022)

TPS4614 Background: Bacillus Calmette-Guérin (BCG) therapy is the standard of care for high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor. However, disease recurrence or progression is common and patients with BCG-unresponsive disease are unlikely to respond to further BCG therapy. In these patients, the current standard of care is radical cystectomy and bladder-preserving treatment options, limited to intravesical chemotherapy or intravenous pembrolizumab. In a phase 1 study, sasanlimab (PF-06801591), a monoclonal antibody to programmed cell death protein 1 (PD-1), was administered subcutaneously at 300 mg every 4 weeks. Sasanlimab had an acceptable safety profile and showed clinical activity aligned to other anti-PD-1/PD-ligand 1 (PD-L1) agents in patients with advanced urothelial carcinoma and non-small cell lung cancer, while offering the convenience of subcutaneous administration. Therefore, CREST Study Cohort B aims to evaluate sasanlimab administered subcutaneously in patients with BCG-unresponsive NMIBC. Methods: CREST Study Cohort B is a non-randomized, multicenter, multinational, open-label, phase 3 study and will enroll ̃160 patients with histologically confirmed BCG-unresponsive, high-risk, non-muscle invasive transitional cell carcinoma of the bladder urothelium (high-grade Ta or T1 tumor, or carcinoma in situ [CIS]) in 2 separate Cohorts, B1 and B2 (̃110 and ̃50 patients, respectively). Cohort B1 will enroll patients with persistent or recurrent CIS with or without concomitant recurrent high-grade Ta/T1 disease, within 12 months of completing adequate BCG therapy. Cohort B2 will enroll patients with recurrent high-grade Ta/T1 disease within 6 months of completing adequate BCG therapy. All patients will receive subcutaneous sasanlimab as a single agent. Efficacy will be assessed at regular intervals by cystoscopy, urine cytology, biopsy, and imaging. The primary endpoint is complete response (CR) and event-free survival (EFS) for Cohort B1 and B2, respectively. Secondary endpoints include duration of CR (Cohort B1 only), EFS (Cohort B1 only), overall survival, time to cystectomy, safety, health-related quality of life, pharmacokinetic parameters, PD-L1 expression, and incidence of anti-drug antibodies. Recruitment of patients in CREST Study Cohort B will be opened in Canada and the United States of America, with other sites in Asia, Australia, and Europe. Clinical trial information: NCT04165317.
Racial/ethnic disparities in serious illness communication for patients with cancer.
Authors: Julia L. Frydman, Laura P. Gelfman, Jose Morillo, Olivia S. Allen, Nina A. Bickell, Deukwoo Kwon, Kathryn I. Pollak, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2022)

6540 Background: Racial/ethnic disparities in serious illness communication exist between patients with cancer and their oncologists. Our prior work has shown that goals of care discussions are three minutes shorter with racial/ethnic minority patients. In this study, we sought to compare oncologist's use of serious illness communication skills, patient participatory behavior, and overall communication quality during encounters with patients with advanced cancer of different self-reported races/ethnicities. Methods: We analyzed baseline recordings from a two-arm multisite randomized controlled trial to test a coaching model of communication skills training for solid tumor oncologists and their newly diagnosed advanced cancer patients. We audio recorded post-imaging patient-oncologist encounters for patients receiving systemic cancer treatment and coded transcripts for oncologist's use of serious illness communication skills (coded as count/encounter): open-ended questions, reflections, empathic responses to patient empathic opportunities, empathic statements, “sorry” statements, and elicitation of questions. We also assessed global codes of oncologist communication (assessed on 5-point Likert scales): flow, concerns addressed, attention, warmth, and respect. Finally, we coded patient participatory behavior (coded as count/encounter): asking questions and assertive responses. We compared the skills and behaviors by race/ethnicity of the patient using the non-parametric Kruskal-Wallis test. Results: We included the 56 (38%) recordings with oncologists who did not receive the intervention. The patients in these encounters were 25 (45%) female; 32 (57%) over the age of 65; 23 (41%) White Non-Hispanic, 20 (36%) Black Non-Hispanic, and 11 (20%) Hispanic. Overall, oncologists responded empathically to patients’ emotions only 19% of the time. Oncologists used fewer reflective statements with Black Non-Hispanic patients (mean 0.3 statements/encounter) as compared to White Non-Hispanic patients (1.1) and Hispanic patients (1.1), p = 0.02. Furthermore, coders rated oncologists as being less likely to address concerns of Black Non-Hispanic patients (mean Likert scale 3.1) as compared to White Non-Hispanic (3.8) and Hispanic (3.4) patients, p = 0.04. Finally, coders rated oncologists as having less warmth with Black Non-Hispanic patients (mean Likert scale 2.9) as compared to White Non-Hispanic (3.8) and Hispanic (3.3) patients, p = 0.04. Conclusions: In this diverse sample of patients with advanced cancer, oncologists used fewer reflective statements, were less attentive to concerns, and expressed less warmth with Black Non-Hispanic patients. Interventions are needed to overcome these striking racial/ethnic disparities in serious illness communication for patients with cancer.